This model provides a method for the prediction, with exaggerated sensitivity, of chemical irritation and proclivity to enhance or retard water barrier repair. We believe that the model may predict the response of low irritation materials and may be more sensitive than patch testing on normal skin, particularly for products to be used on certain areas, e.g. the face, anus, etc., or even mucous membranes. The model must receive extensive use with chemicals of varying properties in order to define its chemical relevance.

Human skin viability can be maintained for absorption studies. It is recommended that this system be used, and that heat-separation and skin freezing not be used, in absorption studies where skin viability and metabolism might be contributing factors to the study.

No abstract

Topical absorption was 6.6% of applied dose. Peak plasma 14C occurred at 30 h after dosing, and peak urinary 14C excretion was at 24-48 h. The urinary 14C excretion pattern exhibits more elimination towards 24 h and beyond, as opposed to early urinary 14C excretion. This suggests a continuous delivery of [14C]-diclofenac sodium from the lotion into and through skin which only ceased when the dosing site was washed. Skin surface residue at 24 h was 26 +/- 9.5% dose (remainder assumed lost to clothing and bedding). Extraction of metabolites from urine amounted to 7.4-22.7% in untreated urine, suggesting substantial diclofenac metabolism to more water soluble metabolites, probably conjugates, which could not be extracted by the method employed. Two Dimensional TLC analysis of untreated urine showed minimal or no diclofenac, again emphasizing the extensive in vivo metabolism of this drug. Treatment of the same urine samples with the enzymes sulfatase and beta-glucuronidase showed a substantial increase in the extractable material. Three spots were consistently present in each sample run, namely diclofenac, 3'hydroxy diclofenac and an intermediate polar metabolite (probably a hydroxylated metabolite). Therefore, there was significant sulfation and glucuronidation of both diclofenac and numerous hydroxy metabolites of diclofenac, but many of the metabolites/conjugates remain unidentified. CONCLUSIONS; There was a continuous delivery of diclofenac sodium from the lotion into and through the skin, which ceased after the dosing site was washed. The majority of the material excreted in the urine were conjugates of hydroxylated metabolites, and not the parent chemical, although further identification is required.

This study suggests that topical agents may accelerate the repair rates of water barrier function in SLS-treated human skin. This model appears facile and robust for evaluating such repair.